In 1983, the United States Food and Drug Administration approved cyclosporin for use in human subjects as an anti-rejection drug. Use of cyclosporin has revolutionized the filed of organ transplant surgery. The drug acts by the inhibition of the body's immune system from mobilizing its vast arsenal of natural protecting agents to reject the transplant's foreign protein. Although cyclosporin is effective in fighting transplantation rejection, it suffers drawbacks in causing kidney failure, liver damage and ulcers which in many cases can be very severe. Accordingly, safer drugs exhibiting less side effects have been investigated.
It was reported that some macrolide compounds, rapamycin and its analogs have immunosuppressive activity or the like (European Patent Publication No. 0184162; U.S. Pat. Nos. 3,929,992 and 3,993,749). European Patent Publication No. 0589703A discloses 21-norrapamycin useful in the treatment or prevention of transplantation rejection, autoimmune diseases and the like. Also, some rapamycin analogs having immunosuppressive activity are disclosed in Japanese Patent Application Laid-Open No. 292948/1993.
The object of the present invention is to provide a novel macrocyclic lactone compound having an excellent immunosuppressive, antimycotic or antitumor activity, and a pharmaceutical composition comprising the same.
Other objects of the present invention are to provide a process for producing the novel macrocyclic lactones, pharmaceutical compositions containing them and methods for using them.